microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis.
miRNA are small noncoding RNA molecules that posttranscriptionally effect mRNA stability and translation by targeting the 3´-untranslated region (3`-UTR) of various transcripts. Thus, dysregulation of miRNA affects a wide range of cellular processes such as cell proliferation and differenti...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-03-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00049/full |
| _version_ | 1818034836561985536 |
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| author | Andrea eNoetel Monika eKwiecinski Natalia eElfimova Jia eHuang Margarete eOdenthal |
| author_facet | Andrea eNoetel Monika eKwiecinski Natalia eElfimova Jia eHuang Margarete eOdenthal |
| author_sort | Andrea eNoetel |
| collection | DOAJ |
| description | miRNA are small noncoding RNA molecules that posttranscriptionally effect mRNA stability and translation by targeting the 3´-untranslated region (3`-UTR) of various transcripts. Thus, dysregulation of miRNA affects a wide range of cellular processes such as cell proliferation and differentiation involved in organ remodelling processes. Divergent miRNA patterns wereobserved during chronic liver diseases of various etiologies. Chronic liver diseases result in uncontrolled scar formation ending up in liver fibrosis or even cirrhosis. Since it has been shown that miR-29 dysregulation is involved in synthesis of extracellular matrix (ECM) proteins, miR-29 is of special interest. The importance of miR-29 in hepatic collagen homeostasis is underlined by in vivo data showing that experimental severe fibrosis is associated with a prominent miR-29 decrease. The loss of miR-29 is due to the response of hepatic stellate cells to exposure to the profibrogenic mediators TGF-β and PDGF-BB. Several putative binding sites for the Smad proteins and the Ap-1 complex are located in the miR-29 promoter, which are suggested to mediate miR-29 decrease in fibrosis. Other miRNA are highly increased after profibrogenic stimulation, such as miR-21. miR-21 is transcriptionally upregulated in response to Smad-3 rather than Smad-2 activation after TGF-β stimulation. In addition, TGF-β promotes miR-21 expression by formation of a microprocessor complex containing Smad proteins. Elevated miR-21 may then act as a profibrogenic miRNA by its repression of the TGF-β inhibitory Smad-7 protein. |
| first_indexed | 2024-12-10T06:45:29Z |
| format | Article |
| id | doaj.art-a71cb7ca37d440cf9907b10b25a7aa54 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-10T06:45:29Z |
| publishDate | 2012-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-a71cb7ca37d440cf9907b10b25a7aa542022-12-22T01:58:41ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2012-03-01310.3389/fphys.2012.0004922382microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis.Andrea eNoetel0Monika eKwiecinski1Natalia eElfimova2Jia eHuang3Margarete eOdenthal4University Hospital CologneUniversity Hospital CologneUniversity Hospital CologneUniversity Hospital CologneUniversity Hospital ColognemiRNA are small noncoding RNA molecules that posttranscriptionally effect mRNA stability and translation by targeting the 3´-untranslated region (3`-UTR) of various transcripts. Thus, dysregulation of miRNA affects a wide range of cellular processes such as cell proliferation and differentiation involved in organ remodelling processes. Divergent miRNA patterns wereobserved during chronic liver diseases of various etiologies. Chronic liver diseases result in uncontrolled scar formation ending up in liver fibrosis or even cirrhosis. Since it has been shown that miR-29 dysregulation is involved in synthesis of extracellular matrix (ECM) proteins, miR-29 is of special interest. The importance of miR-29 in hepatic collagen homeostasis is underlined by in vivo data showing that experimental severe fibrosis is associated with a prominent miR-29 decrease. The loss of miR-29 is due to the response of hepatic stellate cells to exposure to the profibrogenic mediators TGF-β and PDGF-BB. Several putative binding sites for the Smad proteins and the Ap-1 complex are located in the miR-29 promoter, which are suggested to mediate miR-29 decrease in fibrosis. Other miRNA are highly increased after profibrogenic stimulation, such as miR-21. miR-21 is transcriptionally upregulated in response to Smad-3 rather than Smad-2 activation after TGF-β stimulation. In addition, TGF-β promotes miR-21 expression by formation of a microprocessor complex containing Smad proteins. Elevated miR-21 may then act as a profibrogenic miRNA by its repression of the TGF-β inhibitory Smad-7 protein.http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00049/fullFibrosisSmad ProteinsmicroRNAExtracellular Matrix (ECM)Ap1collagens |
| spellingShingle | Andrea eNoetel Monika eKwiecinski Natalia eElfimova Jia eHuang Margarete eOdenthal microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. Frontiers in Physiology Fibrosis Smad Proteins microRNA Extracellular Matrix (ECM) Ap1 collagens |
| title | microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. |
| title_full | microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. |
| title_fullStr | microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. |
| title_full_unstemmed | microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. |
| title_short | microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. |
| title_sort | microrna are central players in anti and profibrotic gene regulation during liver fibrosis |
| topic | Fibrosis Smad Proteins microRNA Extracellular Matrix (ECM) Ap1 collagens |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00049/full |
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